Despite identification of and considerable insights in some of the physiologic variables that influence excretion of Ca and PO4, current understanding is incomplete due to the paucity of data on intratubular effects of most factors (other than parathyroid hormone (PTH), and due to nephron heterogeneity. The role of the juxtamedullary (JM) nephron versus the collecting tubule system in controlling urine Ca and PO4, composition has not been defined. Using clearance and micropuncture techniques, studies are proposed here, in parathyroidectomized Munich-Wistar strain of rats, to define changes in Ca and PO4 transport in both superficial and JM nephrons in response to each of these physiologic variables. Additionally, rats exhibiting Spontaneous Hypercalciuria, recently identified and bred from our laboratory, will be similarly investigated as a model of Idiopathic Hypercalciuria in man. Tubular fluid will be analyzed by the electron microprobe (24). Specifically, these experiments will define the tubular sites of alterations in Ca and PO4 transport: (1) that mediate the hypercalciuria and antiphosphaturi of (a) PO4 depletion and (b) subthreshold hyperglycemia; (2) that result in Spontaneous Hypercalciuria, (3) that produce the calciuric and phosphaturic responses to (a) saline expansion and (b) metabolic acidosis and (4) anticalciuric and phosphaturic phenomena of PTH infusion. Collectively, these data will test the hypothesis that altered rates of transport by JM nephron is one crucial mechanism whereby final urine Ca and PO4 excretion is regulated. Understanding of the complex interplay between the JM nephron and the collecting tubule system will elucidate the physiologic regulation of renal transport of Ca and PO4 and shed light on the pathophysiology in disorders exhibiting inappropriate wastage of PO4 (renal tubular acidosis, diabetic ketoacidosis, hyperparathyroidism) and of Ca (Idiopathic Hypercalciuria, calciuria of metabolic acidosis, PO4 depletion and carbohydrate administration).